The present invention relates to novel tricyclic compounds which strongly antagonize an action of thromboxane A.sub.2 (hereafter referred to as TXA.sub.2) and possess an antiallergic and/or antihistaminic activity.
It is hitherto known that TXA.sub.2 strongly aggregates platelets and is a potent vasoconstrictor [cf. Arachidonic Acid Cascade and Drugs, edited by Shozo Yamamoto, Gendai Iryo Publishing Co., Ltd. (1985)]. Further TXA.sub.2 is a powerful vasoconstrictor against bronchus and bronchial smooth muscle. Therefore, TXA.sub.2 is considered to take part in pathological conditions over a wide range. As examples, the following diseases can be exemplified.
(1) Ischemic disease
For example, myocardial infarction, angina pectoris, and thrombosis
(2) Cerebro-vascular disease
For example, transient ischemic attack, migraine, cerebral hemorrhage, and cerebral infarction
(3) Peripheral vascular diseases and disease caused by unbalanced lipid metabolism
For example, atherosclerosis, capillary convulsion, peripheral circulation disorders, hypertension, and pulmonary embolism
(4) Inflammatory and allergic disease
For example, bronchial asthma, bronchitis, pneumonia, nephritis, and hepatitis
(5) Shock
(6) Cancer metastasis
Accordingly, compounds that antagonize the action of TXA.sub.2 are expected to have therapeutic effects in preventing or treating one or more of the diseases described above or other diseases involving TXA.sub.2. Furthermore, in those instances where use of a particular drug was limited due to side effects mediated by TXA.sub.2 or considered to be mediated by TXA.sub.2, it is expected to alleviate the side effects by the use of compounds which antagonize the action of TXA.sub.2.
In recent years, TXA.sub.2 is also thought to play a role in the pathogenesis of allergic diseases, especially of an asthma (cf. J. Allergy Clin. Immunol., 77, 122 (1986); Arch. Pharmacol., 327, 148 (1984)].
As an antagonist of TXA.sub.2, representative compounds are exemplified in Thrombosis Research, 44, 377 (1986).
Furthermore, an indole compound having the following structure: ##STR2## and the like are disclosed in Japanese Published Unexamined Patent Application No. 249960/1986 [West German Patent Application (DE) No. 3,514,696] and a compound having the following structure: ##STR3## and the like are disclosed in Japanese Publisher Unexamined Patent Application No. 212552/1986 [West German Patent Application (DE) No. 3,508,692]. These compounds have a phenylsulfonamide group as a side chain and exhibit an activity of antagonizing TXA.sub.2.
On the other hand, in tricyclic compounds represented by the following formula: ##STR4## wherein R.sup.0 as a substituent on the aromatic ring has carboxyl or a derivative thereof (for example, an ester, an amide, etc.; hereafter collectively referred to as carboxylic acid group) directly or via an alkylene chain, etc. and W.sup.0 is hydrogen or a substituent such as oxo (.dbd.O), methylene (.dbd.CH.sub.2), hydroxyl, alkoxyl, etc., oxepine derivatives wherein X.sub.1 -X.sub.2 is --CH.sub.2 O--are known as showing antiinflammatory or antiallergic activities, etc. [J. Med. Chem., 19, 941 (1976); ibid., 20, 1499 (1977); ibid, 21, 633 (1978); U.S. Pat. No. 4,282,365 (Japanese Published Unexamined Patent Application No. 21679/1983); U.S. Pat. No. 4,585,788; Japanese Published Unexamined Patent Application Nos. 152673/1986; 152674/1986 and 152675/1986].
Further, it is also known that oxepine derivatives wherein R.sup.0 is hydrogen or a substituent other than the carboxylic acid group, such as, alkyl, alkoxyl, halogen, etc. and W.sup.0 has a (di)alkylaminoalkyl chain via --S-- show antiasthmatic activities [Japanese Published Unexamined Patent Application No. 126883/1983 (EP 0085870A)]. It is also known that derivatives such as oxepine or thiepine (wherein X.sub.1 -X.sub.2 is --CH.sub.2 S--) wherein W.sup.0 is alkylaminoalkylidene show an antidepressant action, etc. [U.S. Pat. Nos. 3,354,155 and 3,420,851; Drugs, 13, 161 (1977); Arz.-Forsch., 13, 1039 (1963); ibid., 14, 100 (1964)]. Furthermore, it is also known that derivatives such as cycloheptene (wherein X.sub.1 -X.sub.2 is --CH.dbd.CH--) or thiepine wherein W.sup.0 has an alkyl chain substituted with an alicyclic nitrogen-containing heterocyclic group such as piperazine, etc. at the terminal thereof via --NHCO-- are known to have a calcium antagonizing activity [Japanese Published Unexamined Patent Application Nos. 47466/1986 (EP 191867A) and 153280/1987].
Further oxepine derivatives having an antiallergic activity wherein R.sup.0 has a carboxylic acid group and W.sup.0 has a (di)alkylaminoalkyl chain via --S-- are known [Japanese Published Unexamined Patent Application Nos. 28972/1985 (U.S. Pat. No. 4,596,804); 152669/1986, 152670/1986, 152671/1986 and 15672/1986 (all of them correspond to EP 188802A); 152676/1986 and 257981/1986]. Furthermore, oxepine or cycloheptene (wherein X.sub.1 -X.sub.2 is --CH.sub.2 CH.sub.2 --) derivatives showing an antihistaminic activity wherein W.sup.0 is a (di)alkylaminoalkylidene are known [Japanese Published Unexamined Patent Application No. 45557/1986 (EP 214779A)]. Still further, oxepine derivatives wherein W.sup.0 is an alkylidene substituted with an alicyclic nitrogen-containing heterocyclic group such as 4-methylpiperazinyl, 4-methylhomopiperazinyl, piperidino, pyrrolidinyl, thiomorpholino or morpholino or with a (di)alkyl-substituted amino at the terminal thereof are known as showing an antiallergic and antiinflammatory activity [Japanese Published Unexamined Patent Application No. 10784/1988 (EP 0235796A)].
Novel and useful TXA.sub.2 antagonists are expected to have preventive and therapeutic effects on various diseases, and are in demand. Further antiallergic agents having a TXA.sub.2 -antagonizing activity are expected to have preventive and therapeutic effects on allergic diseases, and are in demand.